Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

Background The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein. Methods To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns. Results Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-κB-target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells. Conclusions We conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas

Integration approaches for overlapping protected areas in the Qinghai-Xizang Plateau, China

Overlapping protected areas, where the same land is designated as more than one type of protected area, is a widespread issue that complicates the management and effectiveness of the protected area network. Systematically assessing the extent of overlap, along with their effective integration, is crucial for enhancing the effectiveness of protected areas in meeting conservation objectives. We take the Qinghai- Xizang Plateau as a case study, conducting a quantitative assessment of the spatial relationships among six distinct categories of protected areas. We compare the efficacy of two scenarios aimed at integrating overlapping protected areas. Scenario 1 is based on the protection level and categories of protected area and Scenario 2 considers the conservation objectives in addition to Scenario 1. Our findings reveal that 240 (45.6%) protected areas on the Qinghai-Xizang Plateau experience overlap, encompassing about 6.6% of the total area of the protected areas. Notably, over 50% of geo-parks, scenic spots, and forest parks are affected by overlap. While both scenarios yielded comparable outcomes in terms of the overall number and area of integrated protected areas, they differed in their effectiveness across different categories. Compared to Scenario 1, Scenario 2 is more effective in 31 overlapping protected areas that match the conservation objectives. This study offers valuable insights and a reference for China and other nations grappling with the challenges of overlapping protected area designations, which will ultimately improve the efficiency of the protected area network

A Review on Resource Utilization of Spent V-W-Ti Based Selective Catalytic Reduction Catalysts

To address the environmental pollution caused by nitrogen oxides, V2O5-WO3/TiO2 is widely used as a catalyst based on selective catalytic reduction (SCR) technology. However, spent SCR catalysts pose a potential hazard to the environment due to the presence of heavy metals. This problem continues to plague countries with predominantly thermal power generation, and landfills as the dominant disposal method wastes significant metal resources. Previous research into the recovery of these metal resources has received considerable attention. Here, we summarise the methods of recovery and find that research trends are beginning to move towards improving the added value of recovered products. One very promising application is photocatalysts; however, the atomic efficiency of current methods is not satisfactory. Therefore, this review first focuses on the regeneration of spent SCR catalysts and the processes used for elemental extraction to clarify what forms of V, W and Ti can be obtained from existing processes. This is followed by providing directions for the conversion of spent SCR catalysts into photocatalysts with improvements based on such processes. From a different perspective, this also provides a new resource for photocatalysts and is expected to significantly reduce the cost of photocatalyst production

Enhancement of oral bioavailability of quercetin by metabolic inhibitory nanosuspensions compared to conventional nanosuspensions

Quercetin-loaded nanosuspensions (Que-NSps) added metabolic inhibitors were evaluated as drug delivery system to promote the oral bioavailability of quercetin. Que-NSps were prepared respectively using d-alpha tocopherol acid polyethylene glycol succinate (TPGS) or Soybean Lecithin (SPC) as stabilizer. On the basis, Piperine (Pip) or sodium oleate (SO) was, respectively, encapsulated in Que-NSps as phase II metabolic inhibitors. The resulting Que-NSps all displayed a mean particle size of about 200 nm and drug loading content was in the range of 22.3–27.8%. The release of quercetin from Que-NSps was slow and sustained. After oral administration of 50 mg/kg different Que-NSps, the levels of free quercetin in plasma were significantly promoted, the concentration of quercetin metabolites (isorhamnetin and quercetin 3-O-β-d-Glucuronide) were decreased. The absolute bioavailability was, respectively 15.55%, 6.93%, 12.38%, and 23.58% for TPGS-Que-NSps, TPGS-SO-Que-NSps, SPC-Que-NSps, and SPC-Pip-Que-NSps, and 3.61% for quercetin water suspension. SPC-Pip-Que-NSps turned out to an ideal nanocarrier combined nano drug delivery system together with metabolic inhibitor to promote oral absorption of quercetin

Assessing the performance of the pilot national parks in China

The continuous decline of global biodiversity highlights the need for the expansion and improved performance of protected areas (PAs) to achieve the Post-2020 Biodiversity Targets and 2030 Sustainable Development Goals. China proposed the establishment of a national park (NP) system and carried out transformative explorations in 10 pilot NPs, however, it is unclear to what extent the pilot NPs represent China’s biodiversity and resolve management issues. To answer this question, we assessed the performance of the pilot NPs by analyzing the representativeness across typical ecosystems, biodiversity priority areas, and ecosystem services, and by analyzing the management effectiveness of reorganizing the existing PAs and improving the management intensity and man-land relationships. We found that China’s pilot NPs achieved improved representativeness and management effectiveness through range expansion and optimization, institution streamlining, and cohesive management. Compared with the existing PAs, the area of protected typical ecosystems, biodiversity priority areas, and key areas of ecosystem services in the 10 pilot NPs increased by 59.6%, 59.6%, and 54.1% on average, respectively, with a similar land cost overall. The 10 pilot NPs integrated 142 existing PAs of seven categories. The protected areas expanded by 19.4%, and the area under strict protection increased by 42.1%. Additionally, the pilot NPs effectively reduced human disturbance and improved management effectiveness through necessary relocation and enhanced land management. Moving forward, the boundaries and zoning of the NPs should be further optimized, and efforts should be directed to strengthen the governing capacity building, improve the legislation system, increase the financing investment, and promote the value realization of ecological products

Flexible Normal-Tangential Force Sensor with Opposite Resistance Responding for Highly Sensitive Artificial Skin

An electronic skin (e-skin) that can detect both normal and tangential forces with a differentiable signals output is essential for wearable electronics. A flexible, stretchable, and highly sensitive tactile sensor is presented that enables the detection of both normal and tangential forces, with specific opposite and thus easily being differentiated resistance changing outputs. The e-skin, which is based on two-sublayered carbon nanotubes (CNTs)/graphene oxide (GO) hybrid 3D conductive networks, that are anchored on a thin porous polydimethylsiloxane (PDMS) layer, is synthesized via a porogen (GO wrapped NaCl) assisted self-assembling process. The fabricated CNTs/GO@PDMS-based e-skin shows superior sensitivity (gauge factor of 2.26 under a pressure loading of 1 kPa) to tangential force, moderate sensitivity (−0.31 kPa−1 at 0.05–3.8 kPa, and −0.03 kPa−1 at 3.8–6.3 kPa, respectively) to normal force, and a high-reproducible response over 5000 loading cycles including stretching, bending, and shearing. For applications, the e-skin can not only detect wrist pulsing, discriminating different roughness of surfaces, but also produce an obvious responding to an extremely slight ticking

Hydrolytic Modification of SiO2 Microspheres with Na2SiO3 and the Performance of Supported Nano-TiO2 Composite Photocatalyst

Modified microspheres (SiO2-M) were obtained by the hydrolytic modification of silicon dioxide (SiO2) microspheres with Na2SiO3, and then, SiO2-M was used as a carrier to prepare a composite photocatalyst (SiO2-M/TiO2) using the sol-gel method; i.e., nano-TiO2 was loaded on the surface of SiO2-M. The structure, morphology, and photocatalytic properties of SiO2-M/TiO2 were investigated. Besides, the mechanism of the effect of SiO2-M was also explored. The results show that the hydrolytic modification of Na2SiO3 coated the surface of SiO2 microspheres with an amorphous SiO2 shell layer and increased the quantity of hydroxyl groups. The photocatalytic performance of the composite photocatalyst was slightly better than that of pure nano-TiO2 and significantly better than that of the composite photocatalyst supported by unmodified SiO2. Thus, increasing the loading capacity of nano-TiO2, improving the dispersion of TiO2, and increasing the active surface sites are essential factors for improving the functional efficiency of nano-TiO2. This work provides a new concept for the design of composite photocatalysts by optimizing the performance of the carrier

Carbon Nanotube-Modified Fabric for Wearable Smart Electronic-skin with Exclusive Normal-Tangential Force Sensing Ability

It reports a fabric-based flexible electronic skin (e-skin) that differentiates normal pressure from tangential force with opposite resistance response. The e-skin, which is based on multiwall carbon nanotubes (MWNTs) anchored on the fabric surface, is synthesized using a roll-to-roll method by dipping wrinkled fabric into a diluted MWNT/Polydimethylsiloxane dispersion. Normal pressing causes a decrease in resistance (gauge factor of −1.4 KPa−1 at 30–610 Pa), while tangential force leads to an increase in resistance (gauge factor of 1.13 N−1 under a pressure loading of 1 KPa), with good durability observed at over 5000 times of cyclic pressing and tangential force loading. The e-skin is especially insensitive to both bending (<100°) and elongation deformation (<10%) due to the wrinkled surficial structure. For potential applications, the e-skin can not only monitor wrist pulse, sense slight brush friction, but it can also work in a non-contacting mode to detect human breath. Furthermore, because the e-skin can produce opposite resistive responses to both pressure and friction, it can be applied to capture the complete force loading details during the process of picking up an object, which enables potential application for gentle grasping and manipulation of objects on artificial fingertips

Early Pleistocene occurrence of Acheulian technology in North China

Acheulian tools with their associated level of cognizance heralded a major threshold in the evolution of hominin technology, culture and behavior. Thus, unraveling occurrence ages of Acheulian technology across different regions worldwide constitutes a key aspect of understanding the archeology of early human evolution. Here we present a magneto-cyclochronology for the Acheulian assemblage from Sanmenxia Basin, Loess Plateau, North China. Our results place a sequence of stable normal and reversed paleomagnetic polarities within a regional lithostratigraphic context. The Acheulian assemblage is dated to be older than the Matuyama–Brunhes boundary at 0.78 Ma, and is found in strata that are probably equivalent to a weak paleosol subunit within loess layer L9 in the Chinese loess-paleosol sequence, which corresponds to marine isotope stage (MIS) 23, a relatively subdued interglacial period with age range of ∼0.89–0.92 Ma. This age of ∼0.9 Ma implies that Acheulian stone tools were unambiguously present in North China during the Early Pleistocene. It distinctly enlarges the geographic distribution of Acheulian technology and brings its occurrence in North China back into the Early Pleistocene, which is contemporaneous with its first emergence in Europe. Combined with other archeological records, the larger area over which Acheulian technology existed in East Asia during the terminal Early Pleistocene has important implications for understanding early human occupation of North ChinaThis study was supported financially by Chinese Academy of Sciences (Youth Innovation Promotion Program and Key Research Program of Frontier Sciences), the National Natural Science Foundation of China (Grants 41420104008, 41174057, 41290250 and 41290253), the Australian Research Council (DP110105419), the International Partnership Program of Chinese Academy of Sciences (Grants 132B61KYSB20130003 and 132B61KYSB20160003), and the State Key Laboratory of Loess and Quaternary Geology at the Institute of Earth Environment, CAS (SKLLQG 1501 and 1502)